Safety and Superiority of Penicillamine in Radiosensitization of Recurrent Head and Neck Cancer

Sponsor

Nanfang Hospital, Southern Medical University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06103617

Collaborator

(none)

Enrollment

Location

Arm

19.4

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Our preclinical study confirmed that copper accumulation can lead to radioresistance in vitro and in vivo, and reducing the concentration of copper with copper chelator help to overcome radioresistance. Therefore, the investigators plan to carry out a prospective interventional phase II clinical trial to explore the safety and efficacy of penicillamine (a common copper chelator) as a radiosensitizer in the treatment of recurrent head and neck cancer.

Condition or Disease	Intervention/Treatment	Phase
Head and Neck Cancer Recurrent Cancer	Drug: Penicillamine	Phase 2

Detailed Description

Head and neck cancer is the sixth most common cancer worldwide. Radiotherapy is an important measure to control tumor recurrence. Although radiotherapy has been widely used in patients with head and neck cancer, the 2-year local recurrence rate of patients with locally advanced disease is still as high as 50%-60%. This is associated with a lower radiosensitivity in head and neck cancer. High doses of reirradiation (>60 Gy) are associated with severe late complications and treatment-related mortality. Therefore, finding an appropriate sensitizer to improve the radiosensitivity is the key to improve the survival of recurrent patients. Our preclinical study confirmed that copper accumulation can lead to radioresistance in vitro and in vivo, and the results were published in J Hepatol (IF=25.7). Penicillamine is a commonly used copper chelator in clinical practice and can reduce the concentration of copper in the body. Based on this, the investigators plan to carry out a prospective interventional phase II clinical trial to explore the safety and efficacy of penicillamine as a radiosensitizer in the treatment of recurrent head and neck cancer.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Safety and Superiority of Penicillamine in Radiosensitization of Recurrent Head and Neck Cancer: a Single-center, Single-arm, Phase II Clinical Trial

Anticipated Study Start Date :

Oct 20, 2023

Anticipated Primary Completion Date :

Oct 30, 2024

Anticipated Study Completion Date :

Jun 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Penicillamine group Participants in this group are treated with Penicillamine (250mg each time, 4 times per day) during reradiation.	Drug: Penicillamine Participants in this group are treated with Penicillamine (250mg each time, 4 times per day) during reradiation.

Arm

Intervention/Treatment

Experimental: Penicillamine group

Participants in this group are treated with Penicillamine (250mg each time, 4 times per day) during reradiation.

Drug: Penicillamine

Participants in this group are treated with Penicillamine (250mg each time, 4 times per day) during reradiation.

Outcome Measures

Primary Outcome Measures

Objective response rate (ORR) [1 month]
The objective response rate (ORR) is the proportion of patients who achieve a prespecified reduction in tumor volume that is maintained for a minimum duration. The objective response rate was defined as the sum of complete response plus partial response (CR+PR). According to RECIST1.1 criteria, CR was defined as the disappearance of target lesions and the reduction of the short diameter of pathological lymph nodes to less than 10mm. PR: the sum of the measured diameters of the target lesions reduced by 30% compared with the baseline; PD: the sum of the major diameters of all target lesions increased by at least 20%, and the absolute value of the sum of the major diameters increased by more than 5mm, or new lesions appeared. SD: Changes between PR and PD.

Secondary Outcome Measures

Overall survival (OS) [2 years]
OS was defined as the time from the date of inclusion until death from any cause.
local-relapse free survival (LRFS) [2 years]
LRFS was defined as the time from the date of inclusion until tumor relapse.
Incidence of Treatment-Emergent Adverse Events [During treatment and 12 weeks after penicillamine treatment]
treatment-related adverse events will be assessed by CTCAE v5.0

Other Outcome Measures

the biomarkers correlated with ORR, LRFS and OS [2 years]
The correlations between ORR, OS, LRFS and PD-L1 expression in tissues, tumor mutation burden, tumor-related gene changes, plasma cytokines or other biomarkers were explored.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Sign informed consent
The age is 18-75 years
Previously received standard radical radiotherapy or chemoradiotherapy
Head and neck tumors with in situ or cervical lymph node recurrence confirmed by pathological biopsy and imaging examination
ECOG PS：0/1
Laboratory examination confirmed good organ function, which should be carried out within 10 days before the first treatment.

Exclusion Criteria:

After evaluation, it does not meet the indications of re-radiotherapy
Unable to take oral medication
Pregnancy or lactation
Known allergy to penicillamine
Patients who are judged by the researcher as unsuitable to participate in this trial.